Irritable Bowel Syndrome (IBS) is a chronic gastrointestinal disorder characterized by abdominal pain and altered motility. This syndrome is often confused with Inflammatory Bowel Diseases (IBD). IBD and IBS have unknown etiology, and the exact pathogenesis of both remain unknown. Stressful life events exacerbate the symptoms in both IBS and IBD. It appears that stress can change the permeability of colonic epithelium and influence the production of key regulatory cytokines. The central hypothesis of this proposal is that previous intestinal inflammation increases the susceptibility of the colonic epithelium to stress-induced permeability, enabling endotoxins to cross, bind to receptors and cause up regulation of stimulatory neurons. The specific aims of the proposed plan are to 1) measure the effects of previous intestinal inflammation on stress-induced changes en epithelial transport and membrane integrity; 2) determine the effects of previous inflammation on stress-induced changes in cytokine and endotoxin levels; 3) examine the effects of previous inflammation on the involvement of neurokinin receptors in stress-induced changes. These studies will contribute to our understanding of the mechanisms involved in IBS and the possible similarities and differences with IBD. [unreadable] [unreadable] [unreadable]